A Hybrid In Silico/In Vitro Target Fishing Study to Mine Novel Targets of Urolithin A and B: A Step Towards a Better Comprehension of Their Estrogenicity.
17-Hydroxysteroid Dehydrogenases
/ chemistry
Cell-Free System
Computer Simulation
Coumarins
/ chemistry
Enzyme Inhibitors
/ pharmacology
Estradiol Dehydrogenases
/ antagonists & inhibitors
Humans
Ligands
MCF-7 Cells
Models, Molecular
Molecular Docking Simulation
Molecular Dynamics Simulation
Proteins
/ chemistry
Sulfotransferases
/ chemistry
17β-hydroxysteroid dehydrogenase type 1
estrogenic activity
food bioactives
target fishing
urolithins
Journal
Molecular nutrition & food research
ISSN: 1613-4133
Titre abrégé: Mol Nutr Food Res
Pays: Germany
ID NLM: 101231818
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
27
03
2020
revised:
23
06
2020
pubmed:
9
7
2020
medline:
11
9
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
Urolithin A and B are gut metabolites of ellagic acid and ellagitannins associated with many beneficial effects. Evidence in vitro pointed to their potential as estrogenic modulators. However, both molecular mechanisms and biological targets involved in such activity are still poorly characterized, preventing a comprehensive understanding of their bioactivity in living organisms. This study aimed at rationally identifying novel biological targets underlying the estrogenic-modulatory activity of urolithins. The work relies on an in silico/in vitro target fishing study coupling molecular modeling with biochemical and cell-based assays. Estrogen sulfotransferase and 17β-hydroxysteroid dehydrogenase are identified as potentially subject to inhibition by the investigated urolithins. The inhibition of the latter undergoes experimental confirmation either in a cell-free or cell-based assay, validating computational outcomes. The work describes target fishing as an effective tool to identify unexpected targets of food bioactives detailing the interaction at a molecular level. Specifically, it described, for the first time, 17β-hydroxysteroid dehydrogenase as a target of urolithins and highlighted the need of further investigations to widen the understanding of urolithins as estrogen modulators in living organisms.
Identifiants
pubmed: 32640069
doi: 10.1002/mnfr.202000289
doi:
Substances chimiques
Coumarins
0
Enzyme Inhibitors
0
Ligands
0
Proteins
0
urolithin B
0
3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
1143-70-0
17-Hydroxysteroid Dehydrogenases
EC 1.1.-
3 (or 17)-beta-hydroxysteroid dehydrogenase
EC 1.1.1.51
Estradiol Dehydrogenases
EC 1.1.1.62
HSD17B1 protein, human
EC 1.1.1.62
Sulfotransferases
EC 2.8.2.-
estrone sulfotransferase
EC 2.8.2.4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2000289Informations de copyright
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
S. Alfei, F. Turrini, S. Catena, P. Zunin, M. Grilli, A. M. Pittaluga, R. Boggia, Eur. J. Med. Chem. 2019, 183, 111724.
J. M. Landete, Food Res. Int. 2011, 44, 1150.
F. A. Tomas-Barberan, A. Gonzalez-Sarrias, R. Garcia-Villalba, M. A. Nunez-Sanchez, M. V. Selma, M. T. García-Conesa, J. C. Espín, Mol. Nutr. Food Res. 2017, 61, 1500901.
A. Cortes-Martin, R. Garcia-Villalba, A. Gonzalez-Sarrias, M. Romo-Vaquero, V. Loria-Kohen, A. Ramírez-de-Molina, F. A. Tomás-Barberán, M. V. Selma, J. C. Espín, Food Funct. 2018, 9, 4100.
M. Romo-Vaquero, R. Garcia-Villalba, A. Gonzalez-Sarrias, D. Beltrán, F. A. Tomás-Barberán, J. C. Espín, M. V. Selma, J. Funct. Foods 2015, 17, 785.
P. Saha, B. San Yeoh, R. Singh, B. Chandrasekar, P. K. Vemula, B. Haribabu, M. Vijay-Kumar, V. R. Jala, PLoS One 2016, 11, e0156811.
P. Mena, M. Dall'Asta, L. Calani, F. Brighenti, D. Del Rio, Eur. J. Nutr. 2017, 56, 99.
M. A. Avila-Galvez, J. A. Gimenez-Bastida, A. Gonzalez-Sarrias, J. C. Espin, Food Funct. 2019, 10, 3135.
M. A. Nunez-Sanchez, R. Garcia-Villalba, T. Monedero-Saiz, N. V. Garcia-Talavera, M. B. Gómez-Sánchez, C. Sánchez-Álvarez, A. M. García-Albert, F. J. Rodríguez-Gil, M. Ruiz-Marín, F. A. Pastor-Quirante, F. Martínez-Díaz, M. J. Yáñez-Gascón, A. González-Sarrías, F. A. Tomás-Barberán, J. C. Espín, Mol. Nutr. Food Res. 2014, 58, 1199.
G. Aragones, F. Danesi, D. Del Rio, P. Mena, Trends Food Sci. Technol. 2017, 69, 230.
M. V. Selma, D. Beltran, M. C. Luna, M. Romo-Vaquero, R. García-Villalba, A. Mira, J. C. Espín, F. A. Tomás-Barberán, Front. Microbiol. 2017, 8, 1521.
L. Mele, P. Mena, A. Piemontese, V. Marino, N. López-Gutiérrez, F. Bernini, F. Brighenti, I. Zanotti, D. Del Rio, Arch. Biochem. Biophys. 2016, 599, 42.
L. Dellafiora, P. Mena, P. Cozzini, F. Brighenti, D. Del Rio, Food Funct. 2013, 4, 1442.
M. Larrosa, A. Gonzalez-Sarrias, M. T. Garcia-Conesa, F. A. Tomas-Barberan, J. C. Espin, J. Agric. Food Chem. 2006, 54, 1611.
D. G. Skledar, T. Tomasic, M. S. Dolenc, L. P. Masic, A. Zega, Chemosphere 2019, 220, 706.
W. Zhang, J. H. Chen, I. Aguilera-Barrantes, C. W. Shiau, X. Sheng, L. S. Wang, G. D. Stoner, Y. W. Huang, Mol. Nutr. Food Res. 2016, 60, 2387.
H. S. Aiyer, A. M. Warri, D. R. Woode, L. Hilakivi-Clarke, R. Clarke, J. Agric. Food Chem. 2012, 60, 5693.
M. Larrosa, M. T. Garcia-Conesa, J. C. Espin, F. A. Tomas-Barberan, Mol. Aspects Med. 2010, 31, 513.
L. Dellafiora, G. Aichinger, E. Geib, L. Sánchez-Barrionuevo, M. Brock, D. Cánovas, C. DallʼAsta, D. Marko, Food Chem. 2019, 270, 61.
M. Baroni, G. Cruciani, S. Sciabola, F. Perruccio, J. S. Mason, J. Chem. Inf. Model. 2007, 47, 279.
L. Dellafiora, P. Mena, D. Del Rio, P. Cozzini, J. Agric. Food Chem. 2014, 62, 5881.
L. Dellafiora, M. Marchetti, F. Spyrakis, V. Orlandi, B. Campanini, G. Cruciani, P. Cozzini, A. Mozzarelli, Bioorg. Med. Chem. Lett. 2015, 25, 4297.
M. J. Abraham, T. Murtola, R. Schulz, S. Páll, J. C. Smith, B. Hess, E. Lindahl, SoftwareX 2015, 1-2, 19.
R. B. Best, X. Zhu, J. Shim, P. E. Lopes, J. Mittal, M. Feig, A. D. MacKerell Jr., J. Chem. Theory Comput. 2012, 8, 3257.
V. Zoete, M. A. Cuendet, A. Grosdidier, O. Michielin, J. Comput. Chem. 2011, 32, 2359.
L. Dellafiora, G. Galaverna, G. Cruciani, C. Dall'Asta, Food Chem. Toxicol. 2019, 130, 199.
P. Kruchten, R. Werth, S. Marchais-Oberwinkler, M. Frotscher, R. W. Hartmann, Mol. Cell. Endocrinol. 2009, 301, 154.
N. Wale, G. Karypis, J. Chem. Inf. Model. 2009, 49, 2190.
M. D. Williams, T. Nguyen, P. P. Carriere, S. L. Tilghman, C. Williams, Int. J. Environ. Res. Public Health 2016, 13, 36.
W. G. Garbacz, M. Jiang, W. Xie, Adv. Exp. Med. Biol. 2017, 1043, 455.
E. Sonneveld, J. A. Riteco, H. J. Jansen, B. Pieterse, A. Brouwer, W. G. Schoonen, B. van der Burg, Toxicol. Sci. 2006, 89, 173.
D. Poirier, Curr. Med. Chem. 2003, 10, 453.
A. Cassetta, J. Stojan, I. Krastanova, K. Kristan, M. Brunskole Švegelj, D. Lamba, T. Lanišnik Rižner, J. Steroid Biochem. Mol. Biol. 2017, 171, 80.
D. Schuster, L. G. Nashev, J. Kirchmair, C. Laggner, G. Wolber, T. Langer, A. Odermatt, J. Med. Chem. 2008, 51, 4188.
J. D. Brooks, L. U. Thompson, J. Steroid Biochem. Mol. Biol. 2005, 94, 461.
G. S. Chetrite, J. R. Pasqualini, J. Steroid Biochem. Mol. Biol. 2001, 76, 95.
E. Hilborn, O. Stal, A. Alexeyenko, A. Jansson, Oncotarget 2017, 8, 62183.
N. Panth, B. Manandhar, K. R. Paudel, Phytother. Res. 2017, 31, 568.
A. Uifalean, S. Schneider, C. Ionescu, M. Lalk, C. A. Iuga, Molecules 2016, 21, E13.
L. S. Adams, Y. J. Zhang, N. P. Seeram, D. Heber, S. A. Chen, Cancer Prev. Res. 2010, 3, 108.
J. C. Espin, M. Larrosa, M. T. Garcia-Conesa, F. Tomas-Barberan, Evid. Based Complement. Alternat. Med. 2013, 2013, 270418.
B. Pfundstein, R. Haubner, G. Wurtele, N. Gehres, C. M. Ulrich, R. W. Owen, J. Agric. Food Chem. 2014, 62, 10264.
B. Yuan, L. L. Wang, Y. Jin, H. J. Zhen, P. Xu, Y. Xu, C. Li, H. Xu, AAPS J. 2012, 14, 329.
J. P. Piwowarski, I. Stanisławska, S. Granica, J. Stefańska, A. K. Kiss, Drug Metab. Dispos. 2017, 45, 657.